Efficacy of homoeopathic treatment: Systematic review of meta-analyses of randomised placebo-controlled homoeopathy trials for any indication

Background and objective Since 1997, several meta-analyses (MAs) of placebo-controlled randomised efficacy trials of homoeopathy for any indication (PRETHAIs) have been published with different methods, results and conclusions. To date, a formal assessment of these MAs has not been performed. The main objective of this systematic review of MAs of PRETHAIs was to evaluate the efficacy of homoeopathic treatment. Methods The inclusion criteria were as follows: MAs of PRETHAIs in humans; all ages, countries, settings, publication languages; and MAs published from 1 Jan. 1990 to 30 Apr. 2023. The exclusion criteria were as follows: systematic reviews without MAs; MAs restricted to age or gender groups, specific indications, or specific homoeopathic treatments; and MAs that did not assess efficacy. We searched 8 electronic databases up to 14 Dec. 2020, with an update search in 6 databases up to 30 April 2023. The primary outcome was the effect estimate for all included trials in each MA and after restricting the sample to trials with high methodological quality, according to predefined criteria. The risk of bias for each MA was assessed by the ROBIS (Risk Of Bias In Systematic reviews) tool. The quality of evidence was assessed by the GRADE framework. Statistical analyses were performed to determine the proportion of MAs showing a significant positive effect of homoeopathy vs. no significant difference. Results Six MAs were included, covering individualised homoeopathy (I-HOM, n = 2), nonindividualised homoeopathy (NI-HOM, n = 1) and all homoeopathy types (ALL-HOM = I-HOM + NI-HOM, n = 3). The MAs comprised between 16 and 110 trials, and the included trials were published from 1943–2014. The median trial sample size ranged from 45 to 97 patients. The risk of bias (low/unclear/high) was rated as low for three MAs and high for three MAs. Effect estimates for all trials in each MA showed a significant positive effect of homoeopathy compared to placebo (5 of 5 MAs, no data in 1 MA). Sensitivity analyses with sample restriction to high-quality trials were available from 4 MAs; the effect remained significant in 3 of the MAs (2 MAs assessed ALL-HOM, 1 MA assessed I-HOM) and was no longer significant in 1 MA (which assessed NI-HOM). Discussion The quality of evidence for positive effects of homoeopathy beyond placebo (high/moderate/low/very low) was high for I-HOM and moderate for ALL-HOM and NI-HOM. There was no support for the alternative hypothesis of no outcome difference between homoeopathy and placebo. The available MAs of PRETHAIs reveal significant positive effects of homoeopathy beyond placebo. This is in accordance with laboratory experiments showing partially replicable effects of homoeopathically potentised preparations in physico-chemical, in vitro, plant-based and animal-based test systems. Systematic review registration PROSPERO CRD42020209661. The protocol for this SR was finalised and submitted on 25 Nov. 2020 and registered on 26 Dec. 2020. Supplementary Information The online version contains supplementary material available at 10.1186/s13643-023-02313-2.


Methods of the meta-analyses
Suppl.Table 3 Main research objective or question for meta-analyses Author, year Main research objective or hypothesis (quotation source) Linde 1997 "…to assess whether the clinical effect reported in RCTs of homoeopathic remedies equivalent to that reported for placebo" (Abstract) Linde 1998 "…to summarize the actual state of clinical efficacy research on individualised homoeopathy" (Abstract)."…to give an overview of the current state of the approaches, results and problems of the available RCTs on individualised homoeopathy that should be useful for future research" (Discussion) Cucherat 2000 "To establish …whether there is any evidence from RCTs of the efficacy of homoeopathic treatment in patients with any disease" (Abstract) Shang 2005 "We assumed that the effects observed in placebo-controlled trials of homoeopathy could be explained by a combination of methodological deficiencies and biased reporting."(Discussion) Mathie 2014 To test "the hypothesis that the outcome of an individualised homoeopathic treatment approach using homoeopathic medicines is distinguishable from that of placebos".(Abstract) Mathie 2017 To test "the null hypothesis that the main outcome of treatment using a non-individualised (standardised) homoeopathic medicine is indistinguishable from that of placebo" (Abstract) medicine prepared homoeopathically and whose dilution (or that of each of its components) was ≥1X".Mathie 2014-Protocol: "Homoeopathic medicines are also used in other therapeutic approaches such as anthroposophic medicine and homotoxicology, which are not the subject of our review work described below".Mathie 2017-Protocol: Anthroposophic medicine mentioned but not as an exclusion criterion. Suppl.

Secondary outcomes
Suppl.

Table 4
Eligibility criteria for meta-analyses: Design, publication types Sufficient data for calculation of outcome rates.Exclusion: Homoeopathy trials with indications for which no matched trial of conventional medicine could be found.

Table 8
Literature searches *The Boissel 1996 report, on which the Cucherat 2000 paper is based, was published in December 1998.**Individual collections, homoeopathic meetings on WHO ICF Classification System for Levels of Functioning Linked to Health Condition): 1. Mortality; 2. Morbidity, 3. Health impairment; 4. Limitation of activity, 5. Restriction of participation; 6. Surrogate outcome Suppl.Table 10 Definition/description of different homoeopathy types, verbatim citations from the meta-analyses Linde 1998 Use of a single remedy in patients with a conventional diagnosis; use of fixed combinations of several remedies in patients with a conventional diagnosis Shang 2005 No comprehensive, homoeopathic history was taken, all patients received a single, identical remedy Mathie 2017* One or more homoeopathic medicines are administered for standard clinical situations or conventional diagnoses

Table 16
Summary descriptive data on included trials in text or table (excluding design, trial quality and results)

No. Summary descriptive data on trials (0: No, 1: Yes) Linde 1997 Linde 1998 Cucherat 2000 Shang 2005 Mathie 2014
*Multiple responses possible, as trials could be included in more than one meta-analysis.Data extracted from table data in Linde 1998, Mathie 2014, Mathie 2017.No data available for Linde 1997, Cucherat 2000, Shang 2005 Suppl.Table 19 Age groups, gender in trials of the meta-analysis